Synchrotron radiation micro-CT as a novel tool to evaluate the effect of agomir-210 in a rat spinal cord injury model

Brain Res. 2017 Jan 15:1655:55-65. doi: 10.1016/j.brainres.2016.11.015. Epub 2016 Nov 12.

Abstract

MicroRNA-210 (miR-210) was initially reported to be associated with hypoxia and plays a vital role in modulating angiogenesis. However, the potential effect and underlying mechanisms of miR-210 activity in rat spinal cord injury (SCI) have not yet been fully illuminated. In the present study, differential microRNA expression after SCI was determined by Microarray analysis. To explore the effect of miR-210 after SCI, we intrathecally injected agomir-210 with Alzet Osmotic Pumps to up-regulated the endogenous miR-210 expression. Then, synchrotron radiation micro-CT (SRμCT) imaging was used to investigate the effect of agomir-210 in rat SCI model. We found that the endogenous miR-210 expression could be up-regulated by intrathecal agomir-210 injection. The administration of agomir-210 significantly promoted angiogenesis, as evidenced by increased vessel number and volume detected by SRμCT, attenuated the lesion size and improved functional recovery after SCI. Additionally, agomir-210 attenuated cellular apoptosis and inflammation in the injured rat spinal cord. Expression levels of pro-apoptotic protein (Bax) and pro-inflammatory cytokines (TNF-α and IL-1β) were significantly decreased after agomir-210 treatment, whereas expression levels of anti-apoptotic (Bcl-2) and anti-inflammatory (IL-10) proteins were up-regulated. In conclusion, our results indicated that SRμCT is a powerful imaging tool to evaluate the effects of angiogenesis after agomir-210 administration in rat SCI model. The up-regulation of endogenous miR-210 expression following agomir-210 administration promoted angiogenesis and anti-apoptotic protein expression, and attenuated inflammation. MiR-210 played a positive role in neurological functional recovery and could be a potential new therapeutic target for SCI.

Keywords: Angiogenesis; Apoptotic; Inflammation; MiR-210; SRμCT; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiography
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Imaging, Three-Dimensional
  • Injections, Spinal
  • Male
  • MicroRNAs / metabolism
  • MicroRNAs / pharmacology*
  • Microvessels / diagnostic imaging
  • Microvessels / drug effects
  • Microvessels / physiopathology
  • Neuroimmunomodulation / drug effects
  • Neuroimmunomodulation / physiology
  • Neuroprotective Agents / pharmacology*
  • Random Allocation
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Spinal Cord / diagnostic imaging
  • Spinal Cord / drug effects
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / diagnostic imaging*
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology
  • Synchrotrons
  • Treatment Outcome
  • X-Ray Microtomography*

Substances

  • MIRN210 microRNA, rat
  • MicroRNAs
  • Neuroprotective Agents